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An Assignment onGene Therapy Related to Cancer,

AIDS & Hereditary DiseasesPrepared by: Anha Afrin Shefa

Student ID: S!"#""""

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What is Gene Therapy(GT)? Gene therapy is an experimental technique that uses genes to

treat or prevent disease. In the future, this technique mayallow doctors to treat a disorder by inserting a gene into apatients cells instead of using drugs or surgery.

Researchers are testing several approaches to gene therapy,

including:Replacin$a mutated gene that causes disease with a healthy copy of the gene.Inactivating, or !%noc%in$ out," a mutated gene that is functioning improperly.

Introducin$a new gene into the body to help #ght a disease.

Gene therapy was #rst conceptualied in "'().

$he *rst +DA!approed $ene therapy experiment in the %nited&tates occurred in '((), when *shanti +e&ilva was treated for *+*SCID*denosine deaminase de#ciency severe combinedimmunode#ciency-

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Techniques of Gene Delivery

Gene transfer by -atural.ethods are Geneconugation, /acterialtransformation, Retroviraltransduction,

*grovbacterium mediatedtransfer.

Physical .ethodsincludes0icroinection and /iolisticstransformation.

Che.ical .ethods are+1* transfer by calciumphosphate,

2iposome mediated transfer.

/lectrical ethod!

3lectroporation.

Types of 0ectors

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GT for Treatment of Cancer 4ancer causes cells to $ro1 aberrantly. $he growth of

cancer cells leads to damage of normal tissues, causingloss of function.

It is better to have a way of treating the cancer byrepairin$ the faulty $enes or better yet replacin$

the. 1ith functional $enes so that the routine genefunctions are revived. Gene therapy is a way of repairinggenetic problems.

$his can be achieved by addin$ a functional copy ofthe defectie $ene. 5hen a functional copy of a faulty

gene is added, the tissues and organs that might havebeen a7ected by the gene mutations will begin to functionin the right way.

$he gene therapy wor8s better because unli8e other cancertreatments that only treat the sy.pto.sit goes deeper

correcting all the genetic problems.

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Strategies of GT for Cancer Insertion of 2sensitiity2 or suicide3 $ene into the tumor by

introducing the gene that encodes 9&t8 thymidine 8inase gene of the

9erpes simplex virus- 4loc%a$e of the e5pression of onco$enes! by introducing the gene

that encodes antisense ;R*& message.

;illing tumor cells by inserting to5in $enes under the control of atumorspeci#c promoter

Protection of ste. cells from the toxic e7ects of chemotherapythrough introduction of the gene that confers 0+R' multiple drugresistance type '-

Insertion of a 1ild!type tu.or suppressor $ene, for example orthe gene involved in 5ilm? tumor.

4loc%a$eof the mechanisms by which tumors evade i..unolo$icaldestruction, for example by introducing the gene that encodesantisense IG@'insulinli8e growth factor'- message.

/nhancin$ the i..uno$enicityof the tumor by introducing genesthat encode foreign antigens.

3nhancing immune cells to increase anti!tu.or actiitybyintroducing genes that encode cyto8ines.

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Telomerase, Suicide and Oncolytic GeneTherapy Approaches

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Efficacy of GT over ConventionalChemotherapy and Cell Protection

/

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/n anc n$i..uno$enicity of thetu.or

/nhancin$ i..unecells to increase anti!tu.or actiity $umor cells are surgically re.oedfrom the

patient, $ro1in$them in tissue culture andinsertin$ immunostimulatory genes invitro.

$hese cells are then re!in6ectedinto thepatient in an e7ort to induce a signi#cant

systemic immune response that will bothdestroy tumor cells and protect the patient

against a recurrence of the tumor.

*lteration of syngeneic tumors with thegenes that encode I2' b, I2A, I2B, I2C,

$1@a, or rinterferon results in immunologicaldestruction of the tumor cells in vivo.

$ lymphocytes have thecapacity to hone in ontumor tissue. $his propertyhas been used to deliver

cyto8ines directly to tumormasses for human genetherapy.

$he secretion of cyto8ineslocally at the tumor site bythe e7ector $ Dcell willenhance their antitumoractivity and avoid the sidee7ects that result from the

systemic administration ofcyto8ines.

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Gene Therapy for Treatment of AIDS

In addition to improving existing antiretroviraltherapy, there are ongoing e7orts to discoveralternative approaches for treatment of9IE*I+&.

Fne promising alternative approach is genetherapy, in which a gene is inserted into a cellto interfere with viral infection or replication.

Fther nucleic acidbased compounds, such as

+1*, siR1*, R1* decoys, riboymesandapta.ersor proteinbased agents such asfusion inhibitors and inc#nger nucleases canalso be used to interfere with viral replication.

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Gene therapy bylentiiral ector

3arly e7orts in gene therapyfor *I+& have been focused onviral vectors as the delivery of

co.bination of 7 di8erentinhibitory $enesin a singlelentiviral vector that utiliesstem cells in the deliveryprocess. &cientists reportedthat cellderived gene transferis safe and biologically activein 9Iinfected individuals.

/ut, the use of viral vectors forgene delivery poses problemssuch as to5icity,i..uno$enicity, insertion.uta$enesisand limitationswith scaleup procedures.$hese problems haveencouraged the investigation

of nonviral vectors for gene

n en ry anfusionby interfering withproduction of receptors orcoreceptors

94Interfere 1ith

translation andtranscriptionof viralgenes preventingproduction of proteinsand genomic R1*.

-A-

;T/CH

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, and?or C@CR#, the maor cell surface coreceptors responsible for viral entry or /- the various sta$es of theiral replication cycle. 9I replicates by reverse transcription to

form +1* and uses the +1* to produce copies of its mR1* for protein

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T/CH

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